Methamphetamine

General information

Methamphetamine is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo(-)-methamphetamine and dextro(+)-methamphetamine. It was first synthesized from ephedrine in 1893 by the Japanese chemist Nagai Nagayoshi. Crystal methamphetamine was first synthesized in 1919 by Japanese chemist Akira Ogata. Methamphetamine properly refers to a specific chemical substance, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine. It is structurally related to amphetamine, however it crosses the blood-brain barrier more rapidly, due to its relatively high lipid solubility. It produces its effects by increasing levels of the neurotransmitters serotonin, dopamine, and norepinephrine in the brain.

Methamphetamine belongs to the substituted phenethylamine and substituted amphetamine chemical classes. It is related to the other dimethylphenethylamines as a positional isomer of these compounds, which share the common chemical formula C10H15N.

Methamphetamine is a Schedule II stimulant under the Controlled Substances Act, which means that it has a high potential for abuse and a currently accepted medical use (in FDA-approved products). It is available only through a prescription that cannot be refilled. Today there is only one legal meth product, Desoxyn®. It is currently marketed in 5, 10, and 15-milligram tablets (immediate release and extended release formulations) and has very limited use in the treatment of obesity and attention deficit hyperactivity disorder (ADHD).

Physical properties

• Formula C10H15N;
• Molar mass 149.237 g/mol;
• Density 0.9 g/cm3 at 25 °C;
• Melting point 170 - 175 °C (338 - 347 °F) for hydrochloride salt;
• Boiling point 212 °C (414 °F) at 760 mmHg;

Chemical properties

Methamphetamine is a chiral compound with two enantiomers, dextromethamphetamine and levomethamphetamine. At room temperature, the free base of methamphetamine is a clear and colorless liquid with an odor characteristic of geranium leaves. It is soluble in diethyl ether and ethanol as well as miscible with chloroform.Dextrorotatory or dextromethamphetamine (also known as d-methamphetamine) is a stronger central nervous system (CNS) stimulant than levomethamphetamine; however, both are considered to be dependence-forming and addictive when misused and capable of producing similar toxicity symptoms at heavy recreational doses.

In contrast, the methamphetamine hydrochloride salt is odorless with a bitter taste. It has a melting point between 170 and 175 °C (338 and 347 °F) and, at room temperature, occurs as white crystals or a white crystalline powder. The hydrochloride salt is also freely soluble in ethanol and water. In a 2013 study of bioreactors in wastewater, methamphetamine was found to be largely degraded within 30 days under exposure to light.

IUPAC name: (RS)-N-methyl-1-phenylpropan-2-amine

Other names: Batu, Bikers Coffee, Black Beauties, Chalk, Chicken,Feed, Crank, Crystal, Glass, Go-Fast, Hiropon, Ice, Meth, Methlies Quick, Poor Man’s Cocaine, Shabu, Shards, Speed, Stove Top, Tina, Trash, Tweak, Uppers, Ventana, Vidrio, Yaba, and Yellow Bam, Desoxyn, Methedrine, N-methylamphetamine, N,α-dimethylphenethylamine, desoxyephedrine;

Synthesis ways

Racemic methamphetamine may be prepared starting from phenylacetone by either the Leuckart or reductive amination methods. In the Leuckart reaction, one equivalent of phenylacetone is reacted with two equivalents of N-methylformamide to produce the formyl amide of methamphetamine plus carbon dioxide and methylamine as side products. In this reaction, an iminium cation is formed as an intermediate which is reduced by the second equivalent of N-methylformamide. The intermediate formyl amide is then hydrolyzed under acidic aqueous conditions to yield methamphetamine as the final product.

Alternatively, phenylacetone (P2P) can be reacted with methylamine under reducing conditions to yield methamphetamine. This reduction can be carried out with Al/Hg as described here.

Also, P2P can be reduced to methamphetamine with help of NaBH4 by following reactions:

One of the most popular trend of methamphetamine obtaining is reduction of ephedrine, which can be extracted from OTC remedies.

Methamphetamine can be obtained from phenylacetaldehyde for two steps. One of them is included Grignard reagent application.

One of the simplest methamphetamine synthesis is from amphetamine.

d- And l-methamphetamine isomers can be separated with help of d-tartaric acid as described in this method for amphetamine. Procedure is the same.

Analysis and purification

Methamphetamine is frequently cut by caffeine, nootropics such as Cinnarizine, Piracetam and etc, a-PVP, other amphetamine-type stimulants and pharmacy substances. There are several methods to check your amphetamine. The most popular and easiest way is Drugs testing reagents. You can read about other methods inMethmphetamine assessment protocol.

Acid-base extraction (ABE), as a purification method, allows you to get a high-quality drug. Method is useful by reason that it takes available reagents, tools and instruments. Fresh methamphetamine have to be washed by acetone after crystal filtration on a Buchner funnel to clean up them. Also, a final product can be recrystallized with alcohol to obtain large shards of meth. Unfortunately, these methods don’t allow to get rid of caffeine and some pharmaceutical adulterants.

There are pictures of different methamphetamine samples after tests by reagents

Effects and dosage

Subjective effects include motivation enhancement, stamina enhancement, appetite suppression, increased libido, and euphoria. Chronic high-dose use can induce states of anxiety & paranoia, delusions, thought disorganization, psychosis, and violent behavior. It is associated with compulsive redosing, especially when it is vaporized ("smoked") or injected, due to the overwhelming euphoric rush it produces in the user upon initial administration.

Methamphetamine has extremely high abuse and addiction potential; it is widely considered to be one of the most addictive substances due to the intense euphoria it produces. Additionally, unlike amphetamine at therapeutic doses, methamphetamine at moderate to heavy recreational doses is considered to be directly neurotoxic to humans, damaging both dopamine and serotonin neurons within the central nervous system. In nonhuman mammals, degeneration of monaminergic terminals and neuronal apoptosis (cell death) has been known to occur. In humans the effects are also neurotoxic. It also displays cardiotoxicity, including increased blood pressure and elevated risk of stroke and heart attack.

It is highly advised to use harm reduction practices if using this substance.

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• Stimulation - In terms of its effects on the physical energy levels of the user, methamphetamine is usually considered to be extremely energetic and stimulating in a fashion that is identical to that of amphetamine, but stronger than that of modafinil, caffeine, and MDMA. It is similar yet distinct from the stimulation experienced on MDMA, encouraging physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which methamphetamine presents can be described as forced. This means that at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general lack of motor control.
• Physical euphoria - As a potent stimulant, methamphetamine is capable producing states of intense physical euphoria, especially when it is vaporized or injected. However, the initial rush of euphoria can wear off well before the substance has run its course which can promote compulsive redosing, which can have extremely damaging cumulative effects.
• Abnormal heartbeat
• Increased blood pressure
• Increased heart rate
• Appetite suppression
• Body odor alteration - Methamphetamine can potentially leave a very distinct odor within one's urine, sweat and general bodily secretions. Most people would consider it as unpleaseant, but few people do enjoy it and find it a very pleaseant odor.
• Bronchodilation
• Dehydration
• Frequent urination
• Increased bodily temperature
• Increased perspiration
• Muscle contractions
• Muscle spasms
• Neurotoxicity -- from long-term use.
• Stamina enhancement - This effect is more prominent than with any other commonly used stimulant.
• Tactile enhancement
• Tactile hallucination - High doses and/or prolonged usage of certain stimulants like methamphetamine and cocaine can lead to hallucinatory sensations of bugs crawling on the surface of or underneath one’s skin. This is typically referred to as delusional parasitosis or more informally as “meth mites”.
• Teeth grinding
• Temporary erectile dysfunction
• Vasoconstriction
• Pupil dilation
• Vibrating vision - At high doses or certain routes of administration, a person's eyeballs may begin to spontaneously wiggle back and forth in a rapid motion, causing the vision to become blurry and temporarily out of focus. This is a condition known as nystagmus.
• Seizure - This is an uncommon effect but can happen in those predisposed to them, especially while in physically taxing conditions such as being dehydrated, fatigued or undernourished, or if miusing the substance for extended periods of time.

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[SPOILER=Visual effects]

• The visual effects of methamphetamine are usually less consistent and are only mildly noticeable at higher dosages. They are somewhat comparable to the visuals produced by deliriants and are more frequent in darker areas. Scenarios consisting of severe sleep deprivation caused by wakefulness can lead to more intense visual effects and even hallucinations.
• Suppressions
• Double vision
• Distortions
• Visual drifting - This effect is usually subtle or barely noticeable and only occurs at higher dosages or when combined with cannabis. It is most prominent when smoked or taken intravenously and is usually delirious in nature. Commonly this, high dosages or prolonged use can cause level 1-2 visual drifting.
• Brightness alteration
• Hallucinatory states
• Transformations - This effect occurs very rarely, and typically only when the user has taken high doses, is coming down, or has been awake for unusually long periods. They are usually very mild when they do happen to occur.

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[SPOILER=Cognitive effects]

• The cognitive effects of methamphetamine can be broken down into several components which progressively intensify proportional to dosage. The general head space of methamphetamine is described by many as one of extreme mental stimulation, increased focus, ego inflation and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or widespread usage. This particularly holds true during the offset of the experience. The most prominent of these cognitive effects generally include:
• Analysis enhancement
• Compulsive redosing
• Ego inflation
• Cognitive euphoria - This effect is often very intense when compared to other dopaminergic stimulants such as Amphetamine or even Cocaine
• Empathy, affection and sociability enhancement - This effect is mild to moderate and usually disappears within the first few uses or after any form of tolerance has developed.
• Focus enhancement - This component is most effective at low to moderate dosages as anything higher will usually impair concentration.
• Immersion enhancement
• Increased libido
• Increased music appreciation
• Memory enhancement
• Motivation enhancement
• Thought acceleration
• Thought organization
• Time compression - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
• Wakefulness

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[SPOILER=After effects]

• The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
• Anxiety
• Appetite suppression
• Cognitive fatigue
• Depression
• Irritability
• Motivation suppression
• Sleep paralysis - Some users note sleep paralysis after consuming methamphetamine.
• Suicidal ideation
• Thought deceleration
• Psychosis
• Wakefulness - This particular after effect is more pronounced than it is with any other commonly used stimulant.

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Pharmacology

Methamphetamine primarily affects the central nervous system (CNS) by acting as a releasing agent for neurotransmitters such as dopamine, norepinephrine, and serotonin. It also acts as a reuptake inhibitor for some transporter neurons, thereby holding neurotransmitters like norepinephrine in the synapse. Meth also acts as reverse transporter for some transporter neurons, increasing levels of monoamines by forcing the neurotransmitters out of their storage vesicles and expelling them into the synaptic gap by making the dopamine transporters work in reverse. Other mechanisms by which methamphetamine are known to increase monoamine levels are by:

• Decreasing the expression of dopamine transporters at the cell surface, which has the same effect as listed above.
• Increasing cytosolic levels of monoamines by inhibiting the activity of monoamine oxidase (MAO)
• Increasing the activity and expression of the dopamine-synthesizing enzyme tyrosine hydroxylase (TH)

In addition to releasing potent amounts of monoamines, MA has a high lipid solubility which leads to a relatively fast transfer of the drug across the blood-brain barrier and a quick onset in comparison to other stimulants. All of this results in feelings of reward, euphoria, and stimulation as well as an unpleasant offset.

Ilegal market data

Methamphetamine continued to dominate seizures and manufacture of amphetamine-type stimulants at the global level

Data on seizures of ATS (amphetamine-type stimulants) suggest that, at the global level, global trafficking in ATS continues to be dominated by methamphetamine. Seventy-two per cent of ATS seized over the period 2016–2020 was related to methamphetamine, followed by amphetamine (17 percent) and “ecstasy” (4 percent), with the remainder being other ATS*.

The number of countries reporting seizures of methamphetamine rose from 84 in the period 2006–2010 to 117 in the period 2016–2020, suggesting a significant increase in the geographical spread of methamphetamine trafficking. The number of countries reporting seizures of amphetamine and “ecstasy” remained fairly stable between those two periods (91 and 105 countries, and 95 and 103 countries, respectively). Although the total number of countries reporting seizures of ATS has risen, the quantities seized remain somewhat concentrated in certain countries. Three countries accounted for 65 per cent of the global total of methamphetamine seized in the period 2016–2020, three accounted for 54 per cent of “ecstasy” seized, and three accounted for 43 per cent of amphetamine and “captagon” seized. During the period 2016–2020, nearly 16,000 sites and facilities associated with ATS manufacture were dismantled across 45 countries worldwide. Some 94 percent of them were linked to methamphetamine. The majority (69 percent) of the dismantled sites were involved in the actual manufacture of methamphetamine; the others were waste-dumping sites (19 percent) or warehouses used to store chemicals (11 percent). Facilities involved exclusively in the packaging of methamphetamine accounted for less than 1 percent the total, suggesting that most packaging is still done at manufacturing sites.

The manufacture of all major ATS is affected by trends relating to their various precursors and precursors. Once any such chemical substance not under international control is scheduled, chemists at manufacturing sites explore the use of alternatives. As a result, many manufacturing sites produce not only ATS end products but also the precursors required in the manufacturing process. That tends to give a competitive edge to organized crime groups that have, in loco or can afford to hire from abroad, highly qualified chemists.

*Thecategory “other ATS” includes a number of pharmaceutical stimulants, such as methylphenidate, dexamphetamine, phenmetrazine, and Adderall (a trade name for a combination of racemic amphetamine and dextroamphetamine), synthetic cathinones under international control (e.g. methcathinone, mephedrone, methylone or 3,4-methylenedioxypyrovalerone (MDPV), originally often marketed as Bath salts) and non-specified ATS.